It has been demonstrated that CD8 ؉ T cells produce a soluble factor(s) that suppresses human immunodeficiency virus (HIV) replication in CD4؉ T cells. The role of soluble factors in the suppression of HIV replication in monocyte͞macrophages (M͞M) has not been fully delineated.
To investigate whether a CD8؉ T-cell-derived soluble factor(s) can also suppress HIV infection in the M͞M system, primary macrophages were infected with the macrophage tropic HIV-1 strain Ba-L. CD8؉ T-cell-depleted peripheral blood mononuclear cells were also infected with HIV-1 IIIB or Ba-L. HIV expression from the chronically infected macrophage cell line U1 was also determined in the presence of CD8 ؉ T-cell supernatants or -chemokines. We demonstrate that: (i) CD8؉ T-cell supernatants did, but -chemokines did not, suppress HIV replication in the M͞M system; (ii) antibodies to regulated on activation normal T-cell expressed and Secreted (RANTES), macrophage inf lammatory protein 1␣ (MIP-1␣) and MIP-1 did not, whereas antibodies to interleukin 10, interleukin 13, interferon ␣, or interferon ␥ modestly reduced anti-HIV activity of the CD8 ؉ T-cell supernatants; and (iii) the CD8 ؉ T-cell supernatants did, but -chemokines did not, suppress HIV-1 IIIB replication in peripheral blood mononuclear cells as well as HIV expression in U1 cells. These results suggest that HIV-suppressor activity of CD8 ؉ T cells is a multifactorial phenomenon, and that RANTES, MIP-1␣, and MIP-1 do not account for the entire scope of CD8 ؉ T-cell-derived HIV-suppressor factors.
BackgroundAs congenital cytomegalovirus (CMV) infection causes significant clinical consequences not only at birth but also later as neurological sequelae, it is critical to establish a strategy for screening congenitally infected newborns. Previous studies have identified an insufficient sensitivity in screening methods based on the use of dried blood spots (DBSs).ObjectivesTo evaluate the feasibility of the authors' recently developed method for large-scale screening for congenital CMV infection and to identify risk factors for congenital infection.MethodsMore than 21 000 newborns were enrolled at 25 sites in six geographically separate areas of Japan. Urine was collected onto filter cards placed in the diapers, which were then analysed by quantitative PCR using the filter disc directly as a template. Clinical and physical findings of the newborns were extracted from their medical records. CMV strains from the cases and their siblings were genetically compared. Viral loads in DBSs obtained from some of the cases were compared with those in the urine filters.ResultsCongenital CMV infection was identified in 0.31% (95% CI 0.24% to 0.39%) of the newborns, and 30% of the cases (20/66) had typical clinical manifestations and/or showed abnormalities in brain images at birth. Although the positive predictive value of our screening was 94%, the lack of any comparison with a gold standard assay prevented calculation of the negative predictive value. Almost two-thirds of the cases had siblings, a significantly higher frequency than for uninfected newborns. Most of the cases (21/25) excreted CMV strains identical to those of their siblings. CMV DNA was undetectable in three out of 12 retrievable DBS specimens.ConclusionsImplementation of an effective large-scale screening programme for congenital CMV infection is feasible. Siblings are the major risk factor for congenital CMV infection, which emphasises the need for education of mothers-to-be as well as vaccine development.
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